Abstract

Because aerobic metabolic rates decrease in hypoxia-sensitive cells under oxygen-limiting conditions, the demand for glucose or glycogen for anaerobic glycolysis may rise drastically as a means of making up for the energetic shortfall. However, ion and electrical potentials typically cannot be sustained because of energy insufficiency and high membrane permeabilities; therefore metabolic and membrane functions in effect become decoupled. In hypoxia-tolerant animals, these problems are resolved through a number of biochemical and physiological mechanisms; of these metabolic arrest and stabilized membrane functions are the most effective strategies for extending tolerance to hypoxia. Metabolic arrest is achieved by means of a reversed or negative Pasteur effect (reduced or unchanging glycolytic flux at reduced O2 availability); and coupling of metabolic and membrane function is achievable, in spite of the lower energy turnover rates, by maintaining membranes of low permeability (probably via reduced densities of ion-specific channels). The possibility of combining metabolic arrest with channel arrest has been recognized as an intervention strategy. To date, the success of this strategy has been minimal, mainly because depression of metabolism through cold is the usual arrest mechanism used, and hypothermia in itself perturbs controlled cell function in most endotherms.